BME 701 Examples of Biomedical Instrumentation. Hubert de Bruin Ph D, P Eng

Transcription

1 BME 701 Examples of Biomedical Instrumentation Hubert de Bruin Ph D, P Eng 1

2 Instrumentation in Cardiology The major cellular components of the heart are: working muscle of the atria & ventricles specialized conduction cells pacemaker cells 2

3 ECG measurement and analysis (cont.): Analysis of the heart vector is achieved by considering the geometry of the standard leads and the corresponding lead vectors. 3

4 Recorded ECG Signal 4

5 Cardiac Pacemaker 5

6 Other Examples of Electrostimulation Auditory Enhancement/Prosthetics Visual Prosthetics Neuromuscular Control Muscle maintenance 6

7 Prosthetic Advances (Cochlear Implant) 7

8 Cochlear Stimulating Electrode 8

9 Implanted System 9

10 Prosthetic Advances (Visual Artificial Retina) 10

11 Direct Brain Stimulation 11

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13 Rat Muscle Stimulator 5V power isolator From H-bridge 13

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15 Recording Electrophysiological Signals ECG Recording/Computer Analysis EMG Recording/Computer Analysis EEG Recording/Computer Analysis GSR Recording/ Manual Analysis Polygraph Lie Detector Sleep Recording/ Computer Analysis of EEG, ECG, EMG, Respiration, SaO 2 15

16 Instrumentation for Recording from and Stimulating the Brain For therapy or diagnostics Epilepsy Control Movement tremors/rigidity from Parkinsonism Mood disorders ECT, phrenic stimulation, rtms stimulation 16

17 Epilepsy EEG Signal 17

18 Closed Loop Epilepsy Treatment 18

19 Movement Disorders (Parkinsonism) Resulting from loss of neurons in substantia nigra (SNc) which produces dopamine Treated with dopamine agonist (short lived), monoamine oxidase inhibitor (less effective), dopamine precursor L-DOPA (gold standard) Biggest challenge is dose regulation (half-life of L-DOPA is 90 min) Less and less effective as deterioration of substantia nigra continues 19

20 Basal Ganglia 20

21 Deep Brain Stimulation Instead of ablation (to relieve tremor) First reported in 1987 with thalamus stimulation Globus pallidus next site with some success Subthalamic nucleus (1998) most successful with immediate relief of symptoms when stimulator turned on Stimulation of μs pulses at >100 Hz Hypothesized result is inhibition, same as ablation 21

22 Basic Stimulator Medtronic Kinetra Stimulator Treat Parkinson or other Movement Disorders 22

23 System to Control Movement Disorders 23

24 Electrode Insertion 24

25 Electrodes for Depression 25

26 EM Treatment of Depression Acute and Maintenance ECT gold standard? Maintenance (10 treatments) as effective as medication but 46% relapse Vagal Nerve Stimulation (implant) Mixed results Repetitive Transcranial Magnetic Stimulation ( non-invasive ) Mixed Results 26

27 Problems Encountered Complexity of Brain (anatomical, neurophysiological) especially of frontal lobes Treatment mechanisms little understood (animal research suggests some mechanisms but human mostly hypotheses) Hardware well developed and flexible but treatment protocols either too rigid or too flexible Patient selection 27

28 VNS: Vagal Nerve Stimulation Possible Mechanisms Alters CSF concentrations of neurotransmitters (e.g. GABBA) or their metabolites Alters functional activity of orbital frontal cortex, insula, thalamus, hypothalamus, etc. Anticonvulsants have been shown to have therapeutic value in mood disorders 28

29 VNS: Vagal Nerve Stimulation Clinical Results Reduction in epileptic seizures (29,000 Cyberonics implants by 2005) few side effects 21 centre trial for major treatment-resistant depression 222 patients (Rush et al, Biol Psychiatry 2005) After 10 weeks 15% responded ( 50% improvement in HRSD) in treatment group vs 10% responded in sham group (not sig.) Longer term response rates more encouraging 29

30 Cyberonics VNS System Pacemaker similar to cardiac pacemaker Cuff electrodes on left vagal nerve Patient or caregiver parameter adjustment via magnetic field 30

31 Pacemaker and Electrodes 31

32 rtms: Repetitive Trans-Cranial Magnetic Stimulation Treat severely depressed patients who are resistant to pharmacology Alternative is periodic applications of electro-shock (ECT) treatment 30% of patients respond Would like to increase percentage of responders 32

33 Magnetic Nerve Stimulation (MNS) Coil current Induced current Coil current Neural depolarization Neural depolarization 33

34 Current Commercial Machines Example Magstim 34

35 Stimulus Waveforms 35

36 Magnetic Field Source: Medtronic, 2004 Source: Medtronic, 2004 Source: Medtronic,

37 Treatment Protocol Find left thenar (abductor pollicis brevis) motor cortex stimulation point by monitoring M-wave of right thenar muscle Stimulate left frontal lobe (F3) at point 5 cm anterior to this site on a sagittal line Using a fixed % (80 120) of thenar threshold amplitude stimulate at 8 to 10 Hz for fixed periods up to 1800 stimuli; several clinics 3000 stimuli Repeat 4 to 5 times/week for 5 weeks 37

38 Clinical Treatment 38

39 Research Challenges (Objectives) Develop quantitative method for predicting which patients will respond to rtms (use pre treatment EEG parameters, QEEG) Develop quantitative method for determining best site of stimulation Determine effects of changing stimulus amplitude and frequency 39

40 Those with correctable pathophysiology may not respond as standard methods place the coil in the wrong spot (we are not very good at predicting RESPONSE using QEEG) Standard positioning Method incorrectly Places coil here. Magnetic energy is not delivered to the appropriate site Possible site Of correctable dysfunction 40

41 Magnetically Evoked Potentials (MEP) Assume the neural tissue is a stochastic system Require multiple stimuli and synchronous averaging of evoked potentials Heating of EEG electrodes during stimulus train Saturation of amplifiers by magnetic stimulus artifact 41

42 Electrode Materials 3s at 20Hz at 85% intensity, r = -30mm 42

43 rtms Trains of Stimuli Au electrode, 3s at 20Hz at 85% intensity, trains at 0, 60, 120s 43

44 Artifact Blocking Various methods have been used: Low slew rate amplifiers (Thut, 2005, Ives, 2006) First 30ms of signal lost and bandwidth reduced High bandwidth amplifiers (Fuggetta, 2005) First 15ms of signal lost Switching off the amplifiers (Shutter, 2006) First 200ms of signal lost Sample-and-hold circuit (Ilmoniemi, 1997) Works, published results ignore or mask first 10 ms 44

45 Systems Approach Gnd Ch0+ Gain Stage (Instrumentation Amplifier, 10x gain) Sampleand-hold Unity gain buffer LabVIEW DAQ board Ch4 Output Ch0- HPF (1 st order, C=0.1µF, R=10Meg, f 0 =0.16Hz) 2 nd Gain (Noninverting op-amp, 100x gain) LPF (1 st order, C=0.1µF, R=1.6k, f 0 =995Hz) Ch0 Input Magnetic stimulator Input / Output Trigger Lines Digital Trigger Input / Output from Magnetic Stimulator Computer 45

46 8 Channel Average Results 8 Hz, 10 sec, Brodmann 46, 69% max, scale mv 46

47 Sham Response to rtms Clicks 47

48 Muscle Responses during 10 Hz Left-sided Stimulation 48

49 Brain Response to 80 pulses at Left B46 49

50 Brain Response to 60 Pulses at Right B46 50